📄 Archived: 2025-08-31 14:35:08 UTC
🔗 Source: https://papers.lgbt/papers/ghrh

### /ghrh

# ghrh analogs and their potential role as non-hormonal adjuncts for masculinization in male transsexuals

by emily/endocrinemoder/adenine

## abstract

Growth hormone-releasing hormone (GHRH) analogs (which stimulate endogenous growth hormone secretion) have been proposed as an adjunct to gender-affirming hormone therapy (GAHT) for transmasculine people who, despite testosterone therapy, have difficulty achieving a typically male body composition. This narrative review (i) outlines the normal sex differences in muscle mass and fat distribution and the expected changes with masculinizing GAHT, (ii) summarizes metabolic data showing that GHRH analogs (and the resulting increase in growth hormone/IGF-1) can increase lean body mass and reduce visceral fat, and (iii) appraises the limited direct evidence—largely extrapolated from studies in other populations (aging hypogonadal men, HIV-associated lipodystrophy)—alongside anecdotal reports from transgender individuals. Potential endocrine interactions (for example, IGF-1’s synergism with androgens) are discussed, as are practical and ethical considerations for use in transgender care (such as use in adolescents to augment adult height). Safety issues—including fluid retention, insulin resistance and diabetes risk, arthralgias/carpal tunnel syndrome, and the theoretical concern of acromegaly with overuse—are presented with monitoring guidance. Taken together, a daily GHRH analog (e.g. tesamorelin 1–2 mg SC) could help a subset of transgender men achieve greater muscle development and a leaner, more “male” fat distribution, provided careful metabolic and orthopedic surveillance is in place and expectations remain realistic.

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GHRH analogs and their potential role as non-hormonal adjuncts for masculinization in female-to-male transsexuals

Introduction

Gender-affirming hormone therapy for female-to-male (FTM) transgender individuals (transgender men) aims to induce masculinization, including increased muscle mass and strength, reduced body fat, and a shift in fat distribution from a feminine pattern (hips/thighs) to a masculine pattern (abdominal/visceral). Testosterone therapy typically produces significant changes: over the first 1–2 years of GAHT, trans men gain substantial lean body mass (often \~10% increase in muscle area within one year) and lose overall fat mass (around 9–10% reduction). Fat is redistributed away from subcutaneous depots on the hips, thighs, and buttocks toward more visceral and truncal stores, resulting in a larger waist and a smaller hip circumference compared to pre-transition or female controls. In practical terms, transgender men on testosterone notice increased muscularity and strength, a decrease in hip/thigh fullness, and a tendency toward a masculinized body. Long-term studies confirm that trans men on sustained testosterone have higher muscle mass and lower subcutaneous fat than cisgender female averages, and their body composition approaches the cisgender male profile in many respects.

Despite these expected changes, not all individuals achieve the degree of muscular development or fat loss they desire. Factors such as age, genetics, baseline body composition, and lifestyle play major roles. Trans men who begin HRT later in life or who cannot engage in high levels of resistance training may find that their muscle gains plateau below the level typical of cisgender males. Others may observe persistent fat deposits in unwanted areas (e.g. lower abdomen or flanks) or less definition in musculature, even with optimal testosterone levels. Moreover, while testosterone increases visceral fat proportion (as part of the male pattern), excessive visceral adiposity is metabolically undesirable and can be aesthetically concerning if it leads to a “beer belly.” These scenarios have prompted interest in adjunct therapies to further promote a masculine body composition – either by enhancing muscle anabolic processes or by preferentially reducing fat. One such approach is leveraging the growth hormone (GH)/IGF-1 axis through GHRH analogs or secretagogues, to potentially amplify the muscle-building and lipolytic milieu alongside testosterone.

GHRH analogs (e.g. tesamorelin) are peptides that stimulate the pituitary to secrete growth hormone, which in turn raises levels of insulin-like growth factor 1 (IGF-1). In clinical contexts such as HIV-associated lipodystrophy, tesamorelin has been shown to reduce visceral fat accumulation and modestly increase lean body mass. Given that cisgender male puberty involves a surge of GH and IGF-1 (2–3× increase) alongside testosterone – contributing to the adolescent growth spurt and muscle accretion – it is theorized that adding a GH-stimulating therapy in adult trans men might recapitulate some of those pubertal synergistic effects that plain testosterone in adulthood cannot fully achieve. This paper reviews the rationale for using GHRH/GH in FTM therapy, the potential benefits on body composition, the evidence from related populations, and the risks and considerations specific to transgender health. We emphasize that this approach is experimental and off-label; our goal is to inform and guide a cautious discussion on whether a GHRH analog has a place in helping certain transmasculine individuals attain their physical transition goals beyond what standard hormone therapy and lifestyle modifications can provide.

Sex differences in muscle and fat, and GAHT effects

Cisgender men and women differ markedly in body composition. On average, men have greater skeletal muscle mass and lower total body fat percentage than women of the same age and BMI. Men also accumulate fat in a different pattern: more internally as visceral fat around the abdomen and liver, and less on the hips and thighs. Women, especially premenopausal, tend to store fat subcutaneously on the buttocks, hips, and limbs, leading to curvier lower bodies. These differences are driven by hormonal milieu (androgens vs estrogens) and developmental factors. Testosterone is anabolic to muscle and tends to promote visceral (omental) fat deposition, whereas estrogen promotes subcutaneous gluteofemoral fat accumulation and limits visceral fat. In a hypogonadal state (low sex steroids), both muscle mass and bone density are reduced, and fat distribution may skew more toward neutral or feminine pattern due to lack of androgens.

When transgender men begin masculinizing HRT with testosterone, their bodies progressively shift toward the cis-male phenotype. Within the first 6–12 months, significant increases in muscle mass and strength occur. A controlled study reported an average +10.4% increase in muscle cross-sectional area and a corresponding \~9.7% decrease in fat mass after one year on testosterone. Strength (e.g. grip strength) improves in parallel with muscle size gains. Fat redistribution also starts early: trans men often notice waist circumference increasing initially (from visceral fat growth) while fat on hips and thighs diminishes. Over the long term, these changes become more pronounced. Van Caenegem et al. observed that trans men on long-term testosterone had significantly higher lean mass and lower subcutaneous fat than female controls, as well as larger waists and smaller hips. In essence, their body composition had shifted to a more masculine profile: more muscle, relatively less fat, and an android fat distribution.

However, not every trans man will reach the muscularity of a cis man who went through puberty at 14. Factors such as starting age of HRT and baseline fitness matter. A teen trans boy on testosterone undergoes something akin to a normal male puberty and can achieve substantial muscle and bone development. In contrast, a trans man who transitions at, say, 30 or 40, may gain muscle from testosterone but not to the same extent as if that exposure had occurred during adolescent growth – partly because GH/IGF-1 levels decline with age and adult myocytes are less responsive to hypertrophy without intensive exercise stimulus. Additionally, those who cannot partake in vigorous resistance training (due to joint limitations, etc.) or who have genetic predispositions for lower muscle mass may find their gains under testosterone alone to be modest. On the fat side, some trans men (especially if older or overweight at start) might still carry residual gluteofemoral fat in areas like the lower abdomen or thighs even after years of HRT. Others might end up with the worst of both worlds: increased visceral fat (from androgen influence and aging) and stubborn subcutaneous fat pockets, leading to frustration with body shape. This has motivated exploration of adjunct measures like GHRH analogs to further sculpt body composition—by enhancing lipolysis and muscle anabolism—beyond what testosterone can do on its own.

GHRH and GH: mechanism of action and metabolic effects

Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that binds to receptors in the anterior pituitary gland, stimulating the pulsatile release of growth hormone (GH, somatotropin). Synthetic GHRH analogs such as tesamorelin (FDA-approved for HIV lipodystrophy) act on the same receptor to boost the body’s own GH secretion. GH then exerts effects directly and via induction of IGF-1 from the liver and other tissues. The GH/IGF-1 axis plays a key role in body composition regulation: GH is strongly lipolytic (fat-burning) and also anabolic, promoting protein synthesis and cell proliferation in muscles, bones, and organs. During puberty, the synergism between high GH/IGF-1 and sex steroids produces rapid gains in height and muscle. Testosterone actually enhances GH output – indeed, in men with hypogonadism, testosterone replacement significantly increases GH and IGF-1 levels. Conversely, estrogen dampens IGF-1 production (which is one reason adult women have higher GH but lower IGF-1 than men).

The metabolic effects of GH include mobilizing triglycerides from adipose tissue and increasing fat oxidation. GH preferentially reduces visceral adipose tissue; patients with GH deficiency often have increased central fat, which reverses with GH therapy. At the same time, GH promotes an increase in lean body mass, partly by stimulating IGF-1 mediated muscle protein synthesis and increasing water content in muscles (via sodium/water retention). Clinically, in GH-deficient adults or older individuals, GH replacement leads to moderate increases in muscle mass and reductions in fat mass, improving overall body composition. Notably, GH-induced weight changes are not “weight loss” in the traditional sense (since muscle may increase even as fat decreases), but rather a repartitioning of weight toward a more muscular, lower-fat state.

GHRH analogs leverage the body’s natural pulsatile GH release, which may have advantages in safety and tissue selectivity over direct high-dose GH injections. Tesamorelin, for example, given at 2 mg daily, causes a sustained moderate elevation of IGF-1 within the upper physiological range, leading to gradual visceral fat reduction. In HIV-positive patients with abdominal fat accumulation, 6 months of tesamorelin cut visceral fat by ~11% versus baseline (placebo group saw no change) and improved trunk\limb fat distribution. After 12 months, visceral fat was \~18% lower than baseline in those who continued therapy. Importantly, these trials noted preservation of subcutaneous fat (no significant loss of limb fat) and a slight increase in lean body mass in the treatment group. In other words, GHRH/GH can help “shift” body composition by decreasing deep belly fat while maintaining or adding muscle. This is essentially the opposite of what happens with aging or prolonged estrogen exposure, which tends to increase fat and decrease muscle.

Applying this to transmasculine care: by activating the GH/IGF-1 axis, one might amplify the anabolic signals concurrent with testosterone. Testosterone already increases muscle via androgen receptor pathways, but having higher IGF-1 could further enhance muscle fiber hypertrophy and perhaps augment strength gains. (IGF-1 can act as a growth factor for muscle, and it may also synergize with androgens at the muscle nuclear level; experimental data suggest IGF-1 can augment androgen receptor signaling when androgen levels are low, although in a high-androgen environment its role is more to independently stimulate growth.) Additionally, GH might help reduce any lingering feminine fat depots. For example, if a trans man has a persistent fat pad on the lower abdomen or flanks, GH’s lipolytic action could potentially shrink those areas. Visceral fat, which tends to increase on testosterone, might be kept in check by GH analog therapy – essentially mitigating one downside of male-pattern fat distribution. Indeed, metabolism researchers have described GH as moving fat “from an apple to a pear” in some contexts, meaning it reduces the risky visceral “apple” fat. In a transgender man, the goal would not exactly be to create a pear shape (which is feminine), but rather to reduce an overly pronounced belly while preserving fat necessary for health. By increasing subcutaneous fat mobilization for energy, GH can help reveal muscle definition (a leaner look) as long as diet and exercise are aligned.

It must be noted that GHRH/GH is not a magic bullet for masculinization. It will not cause masculinizing changes like facial hair, voice deepening, or genital growth – those are exclusively androgen-driven. What it can do is optimize the milieu for muscle growth and fat loss. Think of it as potentially “supercharging” the second puberty that testosterone initiates: in adolescence, high GH is what allows teenagers (especially boys) to transform so rapidly. In adulthood, GH levels are much lower, so changes with testosterone alone occur more slowly and may be limited. A GHRH analog could, in theory, simulate a pubertal-like GH environment, thereby yielding additional muscle and bone benefits. Indeed, studies in older men have shown that combining testosterone with GH yields greater increases in lean mass and larger fat reductions than testosterone alone. For instance, a randomized trial in men over 65 found that testosterone supplementation increased lean body mass and decreased fat, and adding GH on top led to further improvements in both outcomes. This kind of additive effect underpins the interest in adding GH stimulation in trans men who have suboptimal body composition results from testosterone by itself.

Evidence and experience with GHRH/GH in FTM individuals

To date, no clinical trials have specifically examined GHRH analogs or GH therapy in transgender men for the purpose of enhancing masculinization. The evidence we have is indirect, drawn from other populations and anecdotal reports. Perhaps the most relevant data come from HIV-positive patients with lipodystrophy, where the goal (though not related to gender) is to reduce unwanted visceral fat and improve body shape. As noted, tesamorelin trials in that context demonstrated significant abdominal fat reduction and a small increase in lean mass without serious adverse metabolic effects. This shows the concept of using a GH secretagogue to alter fat distribution is feasible. Another related scenario is bodybuilding and anti-aging medicine: GH (and secretagogues) have been used (legally or illicitly) to increase muscle and reduce fat in cisgender men, albeit with mixed results and risk of side effects. Bodybuilders often report that GH can improve muscle fullness and aid fat loss during cutting phases, which aligns with clinical observations.

In transgender care, there are only sparse case reports or community anecdotes. One endocrinologist (Dr. Will Powers) has noted the theoretical appeal of GH in boosting breast development for trans women and muscle for trans men, but he strongly cautions against routine GH use due to the potential for acromegaly and “hyper-masculinization” side effects if misused. In an online forum, Dr. Powers remarked that while youthful levels of GH likely contribute to better results in younger transitioners, administering high-dose GH to an adult is risky and could lead to unwanted bone/cartilage growth (enlarged jaw, hands, etc.) – ironically causing a coarse, even disfigured appearance rather than the desired masculine enhancement. Thus, no experienced provider has publicly advocated broad use of GH for trans people, and major guidelines (WPATH Standards of Care) make no recommendation to include GH in adult transgender treatment.

Nonetheless, some trans men have experimented on their own or through progressive clinics with GH-related therapies. On discussion boards, individuals have reported using GHRH or GH secretagogues to assist with body recomposition. For example, one transgender man described a trial of sermorelin (a GHRH analog) troches for 3 months, after which he “saw some difference with fat loss and muscle retention,” and then planned to switch to a combination of tesamorelin and ipamorelin (a GH-releasing peptide) to further improve his results. He combined this with diet and exercise, aiming to lose fat and gain muscle concurrently – a goal that is notoriously difficult, but one that GH modulation might support. While this is just a single anecdote, it indicates that at least a subset of transmasculine people are exploring this avenue, reporting subjective improvements in energy and body composition. Another community member on a Q\&A forum asked why GH or IGF-1 aren’t part of transgender HRT regimens; responses highlighted that the risks generally outweigh the benefits for most, and that lifestyle (exercise, adequate protein) can naturally boost GH to some extent. Indeed, Dr. Powers noted in his practice that physically active trans women (who thereby raise their GH output) had better breast growth than sedentary ones, implying a role of GH; by analogy, a trans man who trains intensely will harness natural GH surges to maximize muscle gains without needing exogenous GH.

One area where GH has seen limited medical use in transgender care is in adolescents for height augmentation. If a trans boy has not completed linear growth (bone epiphyses open), some clinicians have considered using growth hormone (often alongside an aromatase inhibitor to prevent estrogen-mediated growth plate closure) to increase final adult height. In cisgender girls with early puberty, blockers plus GH have been used to avoid a very short stature; similarly, a trans boy who might have been destined to a shorter female-height could potentially reach a taller height more in male range by such intervention. However, evidence is mixed: recent cohort studies suggest that pubertal suppression with GnRH analogs and subsequent testosterone may already allow trans boys to achieve height in the male normal range (often ending up only slightly below cis male average, and taller than they would have been as females). The WPATH and Endocrine Society guidelines do not routinely recommend GH for transgender youth, reserving it for cases of proven GH deficiency or extreme short stature, due to cost and uncertain risk/benefit. Ethically, manipulating stature in transgender youth is approached cautiously. Thus, GH therapy for height remains rare and case-by-case in the trans context.

In summary, direct evidence for GHRH/GH benefits in trans men is anecdotal and theoretical at this point. We infer potential benefits from other populations: e.g., older hypogonadal men show improved body comp with GH+T, and HIV patients show reduced visceral fat with GHRH analog. These findings support the idea that a trans man with suboptimal muscle/fat profile could similarly gain an edge from GH stimulation. However, without controlled studies in trans men, we must extrapolate cautiously. Any decision to use such therapy should be individualized, and ideally done in the context of a study or rigorous monitoring. (It is worth noting that an upcoming pilot study by our group is being designed to observe the effects of tesamorelin or similar secretagogues on body composition in transgender men across various ages and stages of HRT, to begin filling this evidence gap.)

Potential endocrine interactions

Introducing GHRH/GH therapy into the hormonal mix of a trans man raises some questions about hormone interactions. Testosterone and GH have a bidirectional relationship: testosterone tends to increase GH/IGF-1 production, and GH can in turn amplify some anabolic effects of testosterone. For instance, testosterone increases muscle fiber size partly via satellite cell activation and protein synthesis; IGF-1 from GH can further stimulate these pathways, potentially yielding greater muscle hypertrophy than testosterone alone. There is also evidence from in vitro and animal models that IGF-1 signaling can up-regulate androgen receptor activity or compensate for low androgen levels. In practical terms, a trans man on a stable dose of testosterone might experience a higher free IGF-1 level with GHRH analog use, which could synergistically improve nitrogen balance and muscle growth. Unlike some adjuncts, GH does not directly alter testosterone or estrogen levels, so it shouldn’t interfere with the primary HRT (indeed, tesamorelin trials in cis men showed no change in sex steroid levels). One consideration is that improved insulin sensitivity or changes in fat mass could affect sex-hormone binding globulin (SHBG) levels slightly, but GH’s net effect on SHBG is variable (some studies show GH may reduce SHBG a bit due to insulin-like effects). A lower SHBG could raise free testosterone fraction, which might be a minor bonus for androgen action – but in trans men already usually at male-range T, this is not very significant.

Another theoretical interaction is with the thyroid axis. GH can increase conversion of T4 to T3 and also increase iodine uptake in thyroid; in some patients, long-term GH therapy has been associated with reduced total T4 and a need for higher thyroid hormone dosing if they are hypothyroid. For a trans man, this would only matter if he also has hypothyroidism or is on thyroid meds; monitoring thyroid function during GH therapy would be prudent as a precaution. GH and cortisol also interact (GH can reduce cortisol binding protein, etc.), but clinically not usually problematic unless there’s adrenal insufficiency.

A positive metabolic interaction: GH analog use in someone with visceral obesity could improve their lipid profile and insulin sensitivity if visceral fat is reduced. Tesamorelin trials noted improved triglyceride and HDL levels alongside fat loss. Many trans men experience weight gain or lipid changes on testosterone (mild increase in LDL, drop in HDL, and if significant visceral fat gain, increased insulin resistance). By mitigating visceral fat, GH therapy might indirectly counter some negative metabolic changes of testosterone. However, GH itself in high doses can cause insulin resistance (discussed below), so there’s a balance.

One important question is whether GH could affect the clitoral/penile growth or other androgen-dependent tissues. GH is known to influence penile growth in adolescence (boys with GH deficiency often have micropenis unless treated), usually in synergy with testosterone. In an adult trans man, genital growth from testosterone largely plateaus after 1–2 years; adding GH at that point is not known to rekindle further growth of that tissue. It might increase local IGF-1, but without androgen receptor activation, IGF-1 alone probably doesn’t enlarge genital tissue significantly. There is no evidence that GH analog would deepen the voice or increase facial hair – those changes are androgen-specific and irreversible by the time GH would be introduced.

If GH therapy were used in a transmasculine person who still has ovaries (and thus some estrogen production unless suppressed), one might wonder if GH could induce any ovarian effects. GH can increase IGF-1 in ovarian tissue and theoretically could influence follicle development, but if the person is on testosterone (which usually induces anovulation and low estrogen), the ovaries are mostly dormant. GH is not known to “awaken” ovarian function in that scenario; in fact, GH has been used adjunctively in fertility treatments for cisgender women to improve egg quality, but not to increase estrogen output per se.

In summary, from an endocrine standpoint, adding a GHRH analog mainly raises IGF-1 and has downstream metabolic effects, but it doesn’t alter levels of testosterone or estradiol. It should not interfere with the masculinizing actions of testosterone – if anything, it complements them. One must monitor insulin sensitivity and thyroid function, but otherwise the hormonal interplay is manageable. It is crucial, of course, that GH analogs are not seen as a replacement for testosterone; they do different things. A trans man absolutely requires androgen for all the primary masculinization; GH cannot substitute for that. Instead, GHRH/GH is purely an adjunct to fine-tune body composition outcomes.

Safety considerations and side effects

Any consideration of GH or GHRH therapy must carefully weigh the safety profile, as systemic growth factors can have significant side effects. The experiences in other populations provide a roadmap of what to watch for:

- Edema and fluid retention: GH has well-known renal effects that lead to sodium retention, causing fluid accumulation in tissues. Many patients on GH (or high-dose GHRH) experience mild peripheral edema – e.g. finger rings fitting tighter, ankle swelling, or a puffy face. Clinical trials report edema rates on the order of 10–20%, depending on dose. In most cases this edema is mild and tolerable, but it can be uncomfortable and can obscure muscular definition (which might frustrate someone taking it for that very reason). More seriously, in individuals with underlying heart issues, GH-induced fluid retention could precipitate hypertension or exacerbate incipient heart failure. GH is contraindicated in patients with acute critical illness for this reason (e.g. it was found to increase mortality in ICU patients, likely due to fluid shifts and metabolic stress). For a generally healthy trans man, the main point is to monitor blood pressure and watch for signs of edema. If significant swelling of ankles or sudden weight gain (>5 lbs of water) occurs, dosing should be reduced or paused. Diuretics are generally not a solution because the effect is continuous; instead, you manage by lowering GH exposure. Importantly, unlike estrogen or some other meds, GH doesn’t typically cause central fluid retention in the lungs unless pushing into frank heart failure, but patients should report any new shortness of breath or exercise intolerance. Usually, fluid retention resolves after stopping therapy.

- Musculoskeletal pain and carpal tunnel syndrome: Along with edema, GH can cause soft tissue swelling that leads to joint pain (arthralgias) and muscle aches in a subset of patients. Carpal tunnel syndrome (compression of the median nerve at the wrist) is a classic side effect of long-term GH excess – it can occur transiently in GH therapy due to swelling of the wrist tissues. Patients might notice tingling or numbness in the fingers, especially at night. In trials, arthralgia and hand/foot tingling are among the most common adverse events, again often dose-dependent. For trans men who might already be engaging in weight training, distinguishing normal post-workout soreness from GH side effect might be tricky, but the pattern (symmetrical joint achiness, nerve tingling) can clue one in. These symptoms usually improve by lowering the dose. It’s notable that in the HIV tesamorelin study, about 15% of participants on drug had joint pain vs \~10% on placebo – so it was somewhat higher but not massive. Carpal tunnel occurred in a small percentage. If a patient develops persistent wrist numbness or severe joint pain, discontinuation is warranted to prevent long-term nerve injury.

- Insulin resistance and diabetes risk: One paradoxical aspect of GH is that while it reduces fat, it can worsen glucose tolerance. GH counteracts the action of insulin (it’s one of the so-called “counter-regulatory” hormones), leading to higher blood sugar levels. In healthy individuals, modest GH elevations usually don’t cause diabetes, but those with predispositions (obesity, pre-diabetes, PCOS, etc.) could see their fasting glucose or A1c rise. Studies have shown that high-dose GH can reduce insulin sensitivity; in acromegaly (pathological GH excess), diabetes is a common complication. In the context of GH therapy for fat loss, doses are much lower than acromegaly levels, and short-term trials of tesamorelin noted no significant change in fasting glucose on average. However, they did exclude people with impaired glucose tolerance from those trials. A meta-analysis of GH/GHRH in HIV patients found a slight trend toward elevated blood sugar in some cases. Therefore, a transgender man considering GH analogs should have baseline metabolic screening. If he is insulin resistant or borderline diabetic, GH could tip him into frank diabetes – caution is advised. Even in metabolically healthy individuals, periodic monitoring of fasting glucose or HbA1c during therapy is recommended. Diet becomes especially important: minimizing simple carbs and focusing on low-glycemic foods can help counteract GH’s anti-insulin effect. If needed, a low dose metformin could be introduced to improve insulin sensitivity (though that has its own considerations). In summary, GH therapy is relatively contraindicated in uncontrolled diabetes. If used, one should ensure the patient’s blood sugars remain in safe range. Any signs of diabetes (excessive thirst, frequent urination, etc.) while on GH should prompt immediate evaluation.

- Acromegaly-like effects (bone and tissue overgrowth): Perhaps the most unique (and feared) potential side effect of chronic GH excess is acromegaly – a syndrome of bony and soft tissue overgrowth. In an adult with closed growth plates, GH cannot make you taller, but it can make your bones heavier and joints larger. The jaw (mandible) can thicken and protrude, the brow ridge may enlarge, fingers and toes widen (patients notice ring or shoe size increasing), and facial features coarsen (bigger nose, thicker lips due to connective tissue growth). Internally, organs like the heart can enlarge, and cartilage in joints can overgrow leading to joint deformities. Acromegaly changes develop insidiously over years of high GH exposure, and some can be irreversible. While the doses contemplated for therapeutic use in trans men are much lower than the levels seen in pathological acromegaly, this risk underscores why we avoid over-treatment. A trans man obviously may welcome some “masculinization” of facial features or hands to an extent – but acromegaly is not the way to achieve that. It tends to create disharmony in features (e.g. an unnaturally large jaw or gaps in teeth from jaw growth, etc.) and is a health hazard. The key is dosing: keeping IGF-1 in the high-normal range should not cause acromegaloid changes. It’s when IGF-1 runs many times the upper limit for extended periods that these occur. Monitoring IGF-1 levels every few months can ensure a patient is not in an excessive range. If any physical changes like those described are noted, therapy should be stopped. It is worth repeating Dr. Powers’ warning succinctly: trying to megadose GH in hopes of more gains is very dangerous and counterproductive. The goal, if used, is to mimic a healthy young adult’s GH levels, not a disease state.

- Neoplasia (cancer) considerations: IGF-1 is a growth factor that can promote cell proliferation. There has long been concern (mostly theoretical and from epidemiology) that higher IGF-1 levels might be associated with increased risk of certain cancers (e.g. colorectal, prostate). Acromegaly patients have a slight increase in colon polyps and maybe cancer. However, GH therapy in GH-deficient patients has not convincingly shown a cancer incidence spike in clinical studies – likely because doses aim for normal range IGF-1. Still, in someone with a history of cancer, especially hormone-sensitive cancers (breast, etc.), physicians are very cautious about prescribing GH. In the trans male context, if the individual has had any malignancy (e.g. a breast cancer prior to transition, which is rare but possible, or a strong family history of cancers), the risk-benefit of GH analog is tilted toward risk. For most healthy trans men, short-term use of GH analog is unlikely to “cause” cancer out of the blue, but this is an area lacking long-term data. It’s wise to adhere to recommended cancer screenings (e.g. colonoscopy at appropriate age) and to discontinue GH if any suspicious symptoms arise. Essentially, while there isn’t evidence of GH analog causing cancer in the HIV trials or others, one should remain vigilant given IGF-1’s role in cell growth.

- Bone density and skeletal effects: Unlike some other adjuncts (e.g. pioglitazone can reduce bone density), GH actually tends to increase bone turnover and can improve bone density over time in GH-deficient individuals. In trans men, testosterone is already helping bone density, and adding GH might further stimulate bone formation. That could be a benefit, especially in older trans men at risk of osteopenia. However, excessive bone turnover might lead to bone or joint pain (as noted above) and even a risk of arthritic changes if joints enlarge. Monitoring bone density isn’t necessary for short-term GH use unless other risk factors are present. One exception: GH use in adolescents (for height) can accelerate epiphyseal fusion if not carefully timed, because GH will spur growth which then, once sufficient estrogen is present, leads to growth plate closure. If GH were used in a teenager, it should be done concurrently with delaying estrogen (with blockers or AIs) to get the height benefit safely. In adults, this is not an issue.

- Other side effects: Headaches can occur on GH, sometimes related to intracranial pressure changes (a very rare side effect is benign intracranial hypertension, mostly in children on high-dose GH). If a patient on GH analog complains of severe headaches with vision changes, that would warrant evaluation (including possibly checking if GH exacerbated any underlying predisposition). GH can also cause fatigue in some (perhaps from altered cortisol metabolism) or, conversely, reports of increased energy (due to improved body composition). Sleep disturbances aren’t common, although GH is normally secreted at night, so taking a GHRH analog in the evening might actually improve deep sleep for some or cause vivid dreams in others. Allergic reactions to peptide injections are rare but possible – injection site redness or itching might occur with tesamorelin in a small percentage. Finally, practical side effects include the burden of daily injections (if using an injectable analog).

Discussion: Efficacy and role in masculinization

The key question is how effective GHRH/GH therapy might be in helping with masculinization outcomes, and for whom would it be most appropriate. Based on the evidence, one can expect gradual changes rather than dramatic transformations. In the HIV trials, the 10–18% visceral fat reduction occurred over 6–12 months. In older men, lean mass gains with GH were on the order of a couple of kilograms over a few months. We can extrapolate that a trans man using a GHRH analog might over 6 months notice that his waist is a bit slimmer (perhaps a reduction in waist circumference of a few centimeters if he had central fat), his muscle definition improves (especially if he’s working out, muscles might appear “fuller” due to increased IGF-1 and slight fluid in muscle), and possibly a small increase in scale weight from added lean mass. If he didn’t change his diet, total weight might stay similar or even rise slightly (since GH can increase appetite in some people, careful diet is needed to avoid overeating which could counteract fat loss). The changes are likely to be subtle month to month – tracking with measurements or body scans (DEXA) would be ideal to quantify progress.

The magnitude of effect will vary by individual. Those who stand to benefit the most are probably:

- Trans men with a higher baseline body fat, especially visceral obesity. GH analogs shine in reducing visceral fat, so someone with a significant belly could see a meaningful reduction. For instance, if a patient has metabolic syndrome with elevated waist circumference, tesamorelin might significantly shrink visceral fat depots, improving both health and appearance (a modestly trimmer waist).
- Older trans men or those with indicators of GH deficiency. GH output declines with age; a trans man in his 50s or 60s on testosterone might have a blunted muscle response partly due to age-related GH decline. Such a person might experience improved vitality and muscle tone with a bit of GH supplementation. In fact, one could measure IGF-1: if it’s low for age, they might be a candidate.
- Trans men who are avid bodybuilders or athletes striving for maximal muscle. While we do not endorse non-medical use, it’s known some bodybuilders (cis and trans) experiment with peptides to gain an edge. In a supervised setting, a trans man who has plateaued in muscle gains despite optimal training and testosterone might see slight further gains with GH – though likely far less than what anabolic steroids or simply changes in training could achieve. GH is not nearly as potent as anabolic steroids for muscle building, but it can assist recovery and allow a bit more hypertrophy in combination with intense exercise.
- Those with “stubborn fat” in feminine areas. Some trans men, especially those who started HRT later, may retain fat in typically female spots (like upper thighs, lower buttocks, lower abdomen “pooch”). GH tends to have a generalized fat-reducing effect but doesn’t specifically target one area over another except favoring visceral vs subQ. However, if overall body fat is lowered, those stubborn areas will eventually shrink. GH could be an adjunct to help with general cutting of fat when combined with diet. Notably, if a person is already quite lean, GH won’t magically sculpt a six-pack; it works best when there is excess fat to mobilize.

GH in transmasculine youth for height deserves brief discussion. Some trans boys (especially those assigned female at birth who are from short-stature families) and their parents might be concerned about height, since male social stature can impact confidence. Standard care is to use puberty blockers to prevent early estrogen-driven growth plate closure, then later introduce testosterone, which will induce a male-like pubertal growth spurt. Often, this results in an adult height closer to male percentile than female. If the height prognosis is still very short (say the child is projected to be 5’0” without intervention), pediatric endocrinologists may consider growth hormone therapy during the blockade phase to boost height velocity. Case series have shown trans boys on GnRH analog + GH can gain additional centimeters, especially if started early in puberty suppression. The ethical consideration is treating “idiopathic” short stature in a context entwined with gender dysphoria – some argue it’s reasonable to align height with affirmed gender, others caution about treating what is not a disease. Regardless, this use of GH is limited to specialized pediatric contexts and is beyond our main scope of improving body comp in adults. It’s mentioned for completeness, as some readers may wonder if GH is ever used in trans care – it is, but narrowly (and even then, WPATH v8 in 2022 made no firm recommendation, leaving it to clinical judgment).

“Issues” with specific aspects of masculinization

One might ask if GH/GHRH therapy could negatively impact any aspects of the masculinization process. For instance, could raising GH/IGF-1 somehow counteract testosterone’s effects? There is no evidence of such antagonism; if anything, they work in concert. Unlike the concern in trans women that adding a metabolic drug might reduce breast growth (e.g. theoretical with pioglitazone affecting aromatase in breast tissue), in trans men there is no parallel concern – GH doesn’t inhibit androgen action. If GH were started very early (before top surgery), one could wonder if it might cause any growth of breast tissue (GH can cause some increase in gland size in acromegaly). But in the absence of estrogen, GH on its own has little effect on breast glandular tissue. It could increase chest muscle and perhaps a bit of subcutaneous fat mobilization, which might even flatten the chest slightly. So no evidence that GH would impede chest masculinization; it might make the pectoral muscles bigger, which could actually improve chest appearance especially post-mastectomy.

Another aspect is voice: GH has no effect on vocal cords or laryngeal cartilage once adulthood is reached (in acromegaly, voice can deepen slightly due to vocal cord thickening, but that’s extreme).

Conclusion

GHRH analogs and growth hormone secretagogues represent a novel, biologically plausible adjunct for transmasculine individuals seeking to further masculinize their body composition beyond what standard testosterone therapy provides. By elevating GH and IGF-1 levels, these agents can promote an “anabolic, fat-burning” internal environment akin to that of a younger male puberty, which in theory can increase muscle mass and reduce visceral fat – changes aligned with masculine physique goals. Early evidence from related contexts (aging hypogonadal men, HIV patients) confirms that GH stimulation can decrease abdominal fat by \~10–20% and add a few percent of lean mass over several months. Anecdotally, some trans men who have tried GHRH/GH have reported favorable shifts in their body fat and muscle definition.

However, due to the lack of direct research in transgender populations and the potential for significant side effects, this approach should be considered experimental and undertaken, if at all, with great caution. Current transgender healthcare guidelines do not include GH therapy as part of standard GAHT. The decision to use it must be highly individualized – reserved perhaps for those who have demonstrable need (e.g. low IGF-1 or extreme difficulty with body composition even after optimizing hormones, exercise, and diet) and who fully understand the risks. Importantly, GHRH/GH is an adjunct to, not a replacement for, testosterone. It will not induce male secondary sex characteristics on its own and should never be used instead of adequate androgen therapy.

If proceeding with a GHRH analog, a prudent regimen would be to start at a low dose and closely monitor the patient’s response. Typical dosages (from clinical use in other conditions):

- Tesamorelin is FDA-approved at 2 mg daily SC injection for visceral fat reduction in HIV patients. This dose raises IGF-1 by about 1.5–2 times baseline. Off-label in trans men, some providers might consider 1 mg daily to start (to test tolerance) then increase to 2 mg if no issues.
- Recombinant human GH (somatropin) for adult GH deficiency is usually dosed around 0.2–0.4 mg (about 0.6–1.2 IU) per day, adjusted to IGF-1 levels. In a non-deficient person, that might be a reasonable “low” dose range to mimic high-normal physiology.
- Alternative secretagogues: Sermorelin (an older GHRH analog) has been used at \~0.1–0.2 mg SC daily at bedtime in anti-aging clinics. CJC-1295 (DAC) with ipamorelin is a combination some use, dosed e.g. 0.1 mg 2–3 times a week (CJC) plus 0.3 mg daily (ipamorelin), aiming for a similar net GH increase. Ibutamoren (MK-677) is an oral GH secretagogue often taken at 10–25 mg per day; it’s not regulated as a drug but some transmasculine individuals have experimented with it as a non-injectable option. These alternatives lack robust safety data but are mentioned in community forums.

Monitoring and precautions:

- Check IGF-1 levels \~1 month after starting and periodically (e.g. every 3–6 months). Aim for IGF-1 not to exceed the age-adjusted normal range (or at most, just slightly above if intending short-term use). If IGF-1 comes back very high, reduce the dose.
- Monitor fasting glucose or HbA1c at baseline, 3 months, 6 months. If any significant rise, re-evaluate therapy – implement dietary changes or discontinue if hyperglycemia is developing.
- Monitor weight, waist circumference, and body composition (if possible via DXA or bioimpedance) to objectively see if the therapy is having the intended effect.
- Ensure the patient maintains a protein-rich diet and regular exercise regimen, as these will maximize benefits and mitigate insulin resistance. Without exercise, GH might mostly cause fat loss but also some lean mass water gain without actual strength improvement.
- Contraindications: active malignancy, uncontrolled diabetes, proliferative retinopathy, active severe illness. Use cautiously or not at all in those with a history of cancer unless the potential benefits far outweigh risks and with oncologist input.
- If the patient has not had top surgery (mastectomy) and is concerned about chest fat, note that GH could actually help reduce fat there as part of overall fat loss, but it won’t remove glandular breast tissue.

“Regimen strategy”: Some users of GH analogs cycle their use. For example, doing 3–6 months on therapy (to coincide with heavy training cycles or “bulking” phases where they want to maximize muscle gained), then stopping for a period. This can potentially reduce long-term side effect accumulation and also allows reassessment of whether the benefits are being retained. Others might use it during a “cutting” phase (calorie deficit) to preserve muscle while losing fat – a scenario where GH is known to help prevent muscle catabolism. On the flip side, stopping GH will lead to IGF-1 returning to baseline within a few weeks, and any visceral fat might gradually creep back if no other changes are made (as seen in the HIV study where fat returned after discontinuation). Thus, some may opt for longer-term low-dose therapy with careful monitoring.

In conclusion, while GHRH analogs like tesamorelin offer an intriguing tool to fine-tune body composition – potentially helping a transgender man achieve a leaner, more muscular build – they are not a mainstream part of treatment at this time. The foundational elements of masculinization remain testosterone therapy, exercise, and nutrition. GHRH/GH-based treatments might benefit a subset of individuals who have plateaued or have metabolic obstacles, but these treatments come with costs and risks that must be weighed on a case-by-case basis.

Typical Dosages and Monitoring Summary:

- Tesamorelin: 2 mg SC once daily (standard dose in studies); often given before bedtime to coincide with natural GH pulse. Some may start at 1 mg to assess tolerance.
- Recombinant GH: \~0.3 mg (≈1 IU) SC daily, titrated to IGF-1 in upper normal range. (Not commonly used in trans men unless GH-deficient; carries higher risk of overshoot if not careful.)
- Peptide combinations (CJC-1295/ipamorelin): e.g. 0.1 mg CJC-1295 with DAC 2×/week + 0.3 mg ipamorelin daily at bedtime
- Oral secretagogues (MK-677): 10–20 mg oral daily; long half-life. (Not FDA-approved; user reports suggest significant appetite increase and water retention can occur.)

When using these, start low and go slow. Evaluate IGF-1 and fasting glucose at \~1 month. Adjust dose if IGF-1 is above desired range or if side effects emerge. Many clinicians would cap therapy at 6–12 months continuous use, then reevaluate need.

- Monitoring: IGF-1 every 3 mo; HbA1c every 3–6 mo; periodic metabolic panel (for glucose and liver enzymes); blood pressure and weight each visit; subjective side effects review each visit. If IGF-1 rises above normal, reduce dose by 50% or pause therapy. If edema or arthralgia become moderate, consider alternate-day dosing or a drug holiday to let symptoms subside.

- Lifestyle: Continue rigorous resistance training and adequate protein (\~1.2–1.5 g/kg body weight) to direct the GH/IGF effects toward muscle. Ensure good sleep hygiene (GH release is tied to deep sleep; fragmented sleep can blunt GH effects). Avoid excessive alcohol (which can suppress GH release acutely).

- Endpoint: Aim for tangible improvements in body composition metrics after 6 months. If none are observed despite compliance (and side effects are manifesting), it’s not worthwhile to continue. If positive results occur, weigh maintaining therapy vs. stopping to see if gains persist with just training.

In the end, the use of GHRH analogs in FTM HRT remains an area of exploratory practice. Further research, including the case series we are initiating, will hopefully shed light on efficacy and safety in this specific population. Until stronger evidence is available, this intervention should be considered only for well-informed, closely monitored patients for whom conventional measures have proven insufficient.

References:

1. Van Caenegem, E. et al. (2015). Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data. Eur J Endocrinol, 172(2):163–71. PMID:25550352

2. Van Caenegem, E. et al. (2012). Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy. J Clin Endocrinol Metab, 97(7):2503–11. PMID:22564669

3. Sattler, F.R. et al. (2009). Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab, 94(6):1991–2001. PMID:19293261

4. Falutz, J. et al. (2010). Effects of tesamorelin (TH9507), a growth hormone–releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two Phase 3 trials. J Clin Endocrinol Metab, 95(9):4291–304. PMID:20554713

5. Glesby, M.J. (2013). Treatment of HIV-associated lipodystrophy (UpToDate review). Quoted in Aetna CPB 0170. – Noted that rhGH reduces fat but causes fluid retention, arthralgias, and can induce hyperglycemia in predisposed patients.

6. Powers, W. (2024). Personal communication – Reddit Q\&A (/r/DrWillPowers). Described observations that high growth hormone levels in adolescence enhance feminization/masculinization, but warned against exogenous GH use due to acromegaly risks (enlarged jaw, hands, etc.).

7. Coleman, E. et al. (2012). Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. Int. J. Transgenderism, 13:165–232. – (No recommendation for growth hormone in transgender treatment).

8. Strange\_Atoms (2013). “AI and Peptides” – Reddit /r/ftm thread. User report of improved fat loss and muscle retention after 3 months on sermorelin, and plan to use tesamorelin+ipamorelin with diet/exercise.

9. Sivakumar, G. et al. (2011). Growth hormone axis drugs for HIV lipodystrophy: a systematic review. HIV Med, 12(8):453–62. – Found GH/GHRH decreased visceral fat (WMD –25 cm²) and increased lean mass (+1.3 kg) vs placebo.

10. Alser, M. & Elrayess, M.A. (2022). From an apple to a pear: moving fat around for reversing insulin resistance. Int J Environ Res Public Health, 19(21):14251. – (Discusses metabolic benefits of shifting visceral to subcutaneous fat).